Table 3.

Drug concentrations measured by LC-MS/MS bioanalysis in orthotopic glioblastoma mice after oral administration of niraparib (35 mg/kg) or Olaparib (50 mg/kg) once daily for 3 Days.

	n	Time since dose, h	Plasma, mean (SD), ng/mL	Normal brain, mean (SD), ng/g	Brain tumor, mean (SD), ng/g	Kp, braina	Kp, uu, braina	Kp, tumorb
Niraparib	9	2	8627 (4863)	688 (305)	7704 (6772)	0.080	0.011	0.893
	9	24	937 (1596)	171 (134)	436 (354)	0.182	0.025	0.465
Olaparib	9	2	2451 (700)	76 (80)	309 (238)	0.031	0.020	0.126
	9	24	23.5 (50.1)	8c	78 (92)d	NC	NC	NC

C_{u, brain, ss}, steady-state unbound drug concentration in brain interstitial fluid; C_{u, plasma, ss}, steady-state unbound drug concentration in plasma; F_u, fraction of unbound drug; K_{p, brain}, brain-to-plasma partition coefficient; K_{p, tumor,} tumor-to-plasma partition coefficient; K_{p, uu, brain}, unbound brain-to-plasma partition coefficient; LC-MS/MS, liquid chromatography–tandem mass spectrometry; NC, not calculated.

^aCalculated as ratio of C_{u, brain, ss} (mean normal brain tissue concentration adjusted for F_u) versus C_{u, plasma, ss} (mean terminal total plasma concentration adjusted for F_u).

^bCalculated as ratio of mean brain tumor total concentration versus mean terminal plasma total concentration.

^cOnly one of nine animals had detectable drug levels.

^dOnly three of nine animals had detectable drug levels.